- Responsible for development and implementation of oncology strategy including selection of biologies of strategic focus and hypothesis generation - Responsible for oncology pipeline, which has included a program in manufacturing, a second program in which the manufacturing candidate has been identified, a program in lead identification, and a program focusing on a novel target- Responsible for oncology division of the company including strategy, budget planning, timelines, due diligence on potential targets, experimental design, project management, and much of business development- Responsibilities have increased to include clinical trial design and clinical synopsis writing; leading pitches and development of slide decks for potential investors and partners; development of clinical development plans and TPPs; and liaising with patent attorneys regarding IP - Responsible for development of GIGA-564 as Program Team Lead, also working with consultants to oversee non-clinical, clinical, and project management- Responsible for GIGA-564 pre-IND and IND including writing, non-clinical development, clinical study design, and some FDA communications- Developed collaboration with NCI for early clinical development of GIGA-564

- Responsible for development and implementation of oncology strategy including selection of biologies of strategic focus and hypothesis generation - Led design and development of a third-generation anti-CTLA-4 antibody, GIGA-564, from hypothesis generation and testing through pre-clinical studies for lead identification to selection of a manufacturing candidate in less than 12 months (bioRxiv, 2021). This candidate has enhanced efficacy and reduced toxicity compared to ipilimumab in pre-clinical models.- Led scRNA-seq project that identified a chemokine that enhances accumulation of mature NK cells within the tumor microenvironment and overcomes resistance to anti-PD-L1 therapy (published in BMCBio)

Co-Director, IMUN 506, Immune MechanismsCo-Director, IMUN 507, ImmunopathologyMember of Penn Institute for Immunology, Immunology Graduate Group and the Gene Therapy and Vaccines Graduate Program

When I was at The Wistar Institute the Stone Laboratory investigated the multiple potential mechanisms of action of anti-CTLA-4 therapies in order to uncover strategies to overcome resistance to these therapies. Overcoming resistance to anti-CTLA-4 therapies would be expected to induce long-term, durable anti-tumor responses in more patients. Our research also had implications on understanding mechanisms leading to irAE. Sanseviero E, O’Brien EM, Karras J, Shabaneh TB, Aksoy BA, Xu W, Zheng C, Yin X, Xu X, Karakousis GC, Amaravadi RK, Nam BT, Turk MJ, Hammerbacher J, Rubinstein MP, Schuchter L, Mitchell TC, Liu Q, Stone EL. Anti-CTLA-4 activates intratumoral NK cells and combined with IL15/IL15Ra complexes enhances tumor control. Cancer Immunol. Res. (2019), 7 (8): 1371-1380.

Found that ICOS signaling allows for differentiation of T follicular helper (Tfh) cells by temporarily inactivating the transcription factor FOXO1. Inactivation of FOXO1 in this setting allows for upregulation of key Tfh genes including CXCR5, BCL6, Pdcd1 (PD1), CCR7, CXCR4, IRF4, Selplg (PSGL1) and MAF. FOXO1 also regulates ICOS expression through a negative feedback loop. I also investigated the mutual regulation of immunity and metabolism. With the graduate student Hannah King I investigated the role of FOXO3 in limiting myelopoiesis. Stone EL, Pepper M, Katayama CD, Kerdiles YM, Lai CY, Lin YC, Yang E, Goldrath AW, Li MO, Hedrick SM. Control of T follicular helper cell differentiation by FOXO1. Immunity. (2015), 42:239-51.Kang H, Corr M, Mansson R, Welinder E, Hedrick SM, Stone EL. Loss of murine FOXO3 in cells of the myeloid lineage enhances myelopoiesis but protects from K/BxN-serum transfer-induced arthritis. PLoS One. (2015), 10(5):e0126728

Investigated the regulation of T cell differentiation and function by the transcription factor FOXO1. I found that FOXO1 is required for regulatory T cell function in vivo, regulates CTLA4 expression and limits T cell differentiation into Tbet+ Th1-like T cells. Kerdiles, Y.M.*, Stone, E.L.*, Beisner, D.R., McGargill, M.A., Ch’en, I.L., Stockmann, C., Katayama, C.D. and Hedrick, S.M. Foxo transcription factors control regulatory T cell development and function. Immunity (2010), 33: 890-904. *Denotes co-first author. My contributions to this study include showing that FOXO1 is required for regulatory T cell function in vivo and identifying a FOXO1 binding site in Ctla4.PREVIEW: Ohkura N, Sakaguchi S. Foxo1 and Foxo3 help Foxp3. Immunity (2010), 33: 835-837.Hedrick, S.M., Hess Michelini, R., Doedens, A.L., Goldrath, A.W. and Stone, E.L. FOXO transcription factors throughout T cell biology. Nat. Rev. Immunol. (2012), 12: 649-41.

o NIH-funded postdoctoral position with mentored teaching at San Diego State University, a minority-serving institutiono Simultaneously exceled at both laboratory and teaching responsibilities

My research during my graduate career led me into various fields including glycobiology, immunology, inflammation biology, host-microbe interactions, endocrinology and behavior.Stone EL, Ismail MN, Lee SH, Luu Y, Ramirez K, Haslam SM, Ho SB, Dell A, Fukuda M and Marth JD. Glycosyltransferase Function in Core 2-Type Protein O-Glycosylation. Mol. Cell. Biol. (2009), 29: 2770-82.Green RS, Stone EL, Tenino M, Lehtonen E, Farquhar MG and Marth JD. Mammalian N-Glycan Branching Protects against Innate Immune Self-Recognition and Inflammation in Autoimmune Disease Pathogenesis. Immunity (2007), 27: 308-320.Ismail MN, Stone EL, Panico M, Lee SH, Luu Y, Ramirez K, Ho SB, Fukuda M, Marth JD, Haslam SM and Dell A. High-sensitivity O-glycomic analysis of mice deficient in core 2 {beta}1,6-N-acetylglucosaminyltransferases. Glycobiology (2011), 21: 89-98.Lee SH, Yu SY, Nakayama J, Khoo KH, Stone EL, Fukuda MN, Marth JD and Fukuda M. Core2 O-glycan structure is essential for the cell surface expression of sucrase isomaltase and dipeptidyl peptidase-IV during intestinal cell differentiation. J. Biol. Chem. (2010), 285:37683-92.

o Purified several hundred antibodies and Fc-fusion proteins, many to high purityo Developed a method to remove endotoxin from antibody and Fc-fusion protein preparationso Analyzed antibodies and Fc-fusion proteins by LAL, SDS-PAGE gels, Western blotting and HPLC